ABSTRACT Periodontitis, initiated by bacterial infection and compounded by host inflammatory response, is a leading cause of tooth loss affecting welfare of 65 million US adults. Mounting evidence suggests periodontitis is also associated with systemic health, mostly through a common link, inflammation. Therefore, diagnosis and treatment of periodontal inflammation would potentially improve general health. Current clinical measures of periodontal inflammation are visual inspection and ?bleeding on probing (BOP)?. Unfortunately, they are subjective and insensitive to detect disease activity. Targeted imaging of subclinical signs of inflammation, e.g. increased vascularity, interstitial fluid and tissue loss, etc., would shed light on precise diagnosis and timely treatment of this deliberating disease non-invasively at chairside. Some quantitative ultrasound biomarkers, e.g. backscatter, elasticity, color flow, and power Doppler have been investigated extensively in medicine in recent years and have been recognized as validated for evaluating inflammation of specific body organs. They would be potential candidates to measure periodontal inflammation objectively. A miniature sized (16.2 mm), high-imaging resolution (~60 m) ultrasound probe prototype was developed by our group specifically for use in the constrainted oral cavity and has been validated for accurately imaging periodontal tissues. It is ready for use on a commercially available ultrasound system for collecting the above-mentioned quantitative ultrasound parameters. The hypothesis driving this proposal is that non-invasive and quantitative ultrasound can be used to estimate degree/extent of periodontal inflammation that could eventually lead to early detection of periodontal attachment and bone loss. The aims of this proposal are two folds: (1) Establish quantitative ultrasound based imaging biomarkers, i.e., B-mode (Quantitative Ultrasound, QUS), tissue strain as well as fractional blood volume using phantoms with known properties and (2) Perform correlation testing for determining inflammation extent/severity between the non-invasive ultrasound imaging biomarkers and the invasive histology/molecular biology, using an established preclinical porcine model. Successful outcomes of this investigation will lead to novel, objective and precise ultrasound biomarkers that can estimate severity/extent of periodontal inflammation. Subsequently, the predictability of detecting disease activity individually and collectively will be evaluated through longitudinal preclinical and human studies. Ultimately, we intend to develop clinical guidelines and a clinical imaging protocol for routine oral care to alleviate the tremendous burden of periodontitis affecting millions of US adults.